Diabetes mellitus is a rapidly escalating global health concern, known not only for its metabolic complications but also for its wider impact on quality of life and reproductive health. While earlier studies have hinted at a connection between diabetes and male infertility, the biological mechanisms underlying this association have remained poorly understood. To address this gap, researchers led by Yanan Hao from The Institute of Brain Science and Brain-inspired Research, Shandong First Medical University, and Shandong Academy of Medical Sciences, Jinan, conducted a systematic review and meta-analysis focusing on inflammation as a potential mediator.
The investigators conducted an extensive literature search across the Web of Science, Embase, and PubMed databases, encompassing studies published between 1972 and 2022. Following PRISMA guidelines, they screened hundreds of publications examining the relationship between diabetes and male infertility. Ultimately, eight studies on type 1 diabetes and nine studies on type 2 diabetes met the inclusion criteria for quantitative analysis. In parallel, the team reviewed studies related to inflammation to explore the mechanistic links between diabetes, inflammatory processes, and impaired male fertility.
Key Findings:
- Pooled analysis showed that men with diabetes had a significantly higher risk of infertility compared with non-diabetic men.
- Stratified analysis indicated that type 2 diabetes was more strongly associated with impaired male fertility than type 1 diabetes.
- The stronger association in type 2 diabetes suggests that its metabolic and inflammatory environment may have a greater negative impact on reproductive function.
- The included studies demonstrated low between-study heterogeneity, strengthening the reliability of the overall results.
- Inflammatory biomarkers, including tumor necrosis factor-alpha (TNF-α), were consistently linked to diabetes-related reproductive dysfunction.
- Elevated inflammatory marker levels pointed to chronic, low-grade inflammation as a potential disruptor of normal spermatogenesis and hormonal regulation.
To further support this hypothesis, the researchers incorporated transcriptomic data analyses. These analyses identified enrichment of inflammation-related biological pathways and altered expression of genes critical for male fertility in diabetic conditions. Together, these molecular signatures reinforce the idea that inflammatory processes play a central role in mediating the adverse effects of diabetes on male reproductive health.
The authors conclude that diabetes, particularly type 2 diabetes, poses a significant risk to male fertility, largely through inflammation-driven mechanisms. They suggest that future research should focus on anti-inflammatory strategies as potential therapeutic options for managing infertility in men with diabetes. Targeting chronic inflammation may not only improve reproductive outcomes but also contribute to better overall disease management in this growing patient population.
Reference:
Hao Y, Yang Z, Feng Y, Zhao Y and Ren Y (2025) Inflammation-mediated effects of diabetes mellitus on male fertility: a systematic review and meta-analysis. Front. Endocrinol. 16:1600565. doi: 10.3389/fendo.2025.1600565
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